Method of treating a cancer patient without the need for a tissue biopsy

Abstract

Provided herein, among other things, is a method of treating a cancer patient without the need for a tissue biopsy. In some embodiments, the method may comprise (a) performing or having performed a sequencing assay on cell-free DNA (cfDNA) from a sample of blood from the patient to determine if the cell-free DNA comprises actionable and/or non-actionable sequence variations in one or more target genes, and (b) treating the patient using the following method: i. administering a therapy that is targeted to an actionable sequence variation if the patient is identified as having the actionable sequence variation, and ii. administering a non-targeted therapy in the absence of any follow-up genetic testing on DNA extracted from a tissue biopsy if one or more non-actionable sequence variations and no actionable sequence variations are identified.

What is claimed is: 
     
       1. A method of treating a cancer patient without the need for a tissue biopsy, comprising:
 (a) performing or having performed a sequencing assay on cell-free DNA (cfDNA) from a sample of blood from the patient to determine if the cell-free DNA comprises actionable and non-actionable sequence variations in one or more target genes, 
 wherein:
 (i) an actionable sequence variation is a sequence variation for which there is a therapy that targets the protein encoded by the gene having the sequence variation; and 
 (ii) a non-actionable sequence variation is a sequence variation for which there is no therapy that targets the protein having the sequence variation; 
 
 (b) determining that the cfDNA has no actionable sequence variations; 
 (c) confirming that there are no actionable sequence variations in the cfDNA by identifying non-actionable sequence variations in the cfDNA; and then 
 (d) administering a therapy that does not target a protein encoded by a gene having an actionable or non-actionable sequence variation to the patient, 
 wherein the decision to administer the therapy of step (d) is made without considering data obtained from a tumor biopsy. 
 
     
     
       2. The method of  claim 1 , wherein the non-actionable sequence variations identified in step (c) are statistically unlikely to occur in the same patient as the actionable sequence variations of step (c). 
     
     
       3. The method of  claim 1 , wherein the cancer patient has non-small cell lung cancer. 
     
     
       4. The method of  claim 1 , wherein the target genes assessed for actionable sequence variations comprise EGFR, ALK, ROS1, and BRAF. 
     
     
       5. The method of  claim 4 , wherein:
 i) the actionable variations in EGFR are activating mutations; 
 ii) the actionable variations in ALK include ALK gene fusions; 
 iii) the actionable variations in ROS1 include ROS1 gene fusions; and 
 iv) the actionable variations in BRAF are activating mutations. 
 
     
     
       6. The method of  claim 5 , wherein:
 i) the actionable variations in EGFR comprise L858R, exon 19 deletion, L861Q, G719X, p.S7681, V765A, T783A, V774A, S784P, and L861X or any combination thereof; 
 ii) the actionable variations in ALK comprise EML4-ALK, TFG-ALK and KIF5B-ALK fusions or any combination thereof; 
 iii) the actionable variations in ROS1 comprise CD74-ROS1, SLC34A2-ROS1, SDC4-ROS1 and EZR-ROS1 fusion or any combination thereof; and 
 iv) the actionable variations in BRAF include V600E, L601G, K601E, L597V/Q/R and G469V/S/R/E/A or any combination thereof. 
 
     
     
       7. The method of  claim 1 , wherein the method further comprises:
 calculating the allele frequencies of the non-actionable sequence variations identified in step (c); and 
 calculating the probability that there are no actionable sequence variations in the cfDNA based on the allele frequencies of the non-actionable sequence variations. 
 
     
     
       8. The method of  claim 1 , further comprising:
 analyzing white blood cell DNA from the patient; 
 determining whether any of the actionable or non-actionable sequence variations are due to hematopoiesis of indeterminate potential or a germ-line variation; and 
 eliminating sequence variations that are due to hematopoiesis of indeterminate potential or a germ-line variation from the analysis of steps (b) and (c). 
 
     
     
       9. The method of  claim 1 , wherein the protein that is encoded by the gene that has the actionable sequence variation is a kinase and the therapy is a kinase inhibitor. 
     
     
       10. The method of  claim 1 , wherein the therapy administered in (d) is a platinum-based chemotherapy.